title: Inhibitory effects of meta-iodo-benzylguanidine (MIBG) on endothelial histamine receptor binding.
abstract: Meta-iodo-benzylguanidine (MIBG), a selective inhibitor of mono-ADP-ribosylation, has been shown to inhibit histamine induced inositol-trisphosphate and prostacyclin production. The purpose of this study was to evaluate the effect of MIBG on the binding of histamine to the H1-receptor and to study its effects on phospholipid metabolism in human endothelial cells. The effects of MIBG and MIBA (meta-iodo-benzylamine), which does not affect cellular ADP-ribosylation, on agonist induced cGMP production in cultured HUVEC's were measured by RIA and a binding study carried out to evaluate their effects on the binding of [3H]mepyramine to membrane fractions. MIBG (0.3 mM) reduced histamine induced cGMP production by 90.8% but did not inhibit the cGMP production induced by other agonists. MIBA had no effect. MIBG also reduced the binding of [3H]mepyramine (1.0 nM) to membrane fractions with IC50 at 0.094 mM and maximal inhibition (83%) at 0.22mM MIBG. The calculated Ki was 0.076mM. MIBG and MIBA altered phospholipid metabolism in a similar way as the cationic amphiphilic drug propranolol. MIBA caused up to 42% reduction in [3H]mepyramine binding, probably due to its inhibition of nonspecific binding. These results indicate that MIBG reduces histamine induced cGMP production by inhibiting its binding to H1-receptors and alters phospholipid metabolism in cultured endothelial cells in a similar way as known cationic amphiphilic drugs.
authors.affiliation: Department of Pharmacology, University of Iceland, Reykjavík.
authors.forename: O
authors.initials: O
authors.lastname: Jónsson
authors.forename: H
authors.initials: H
authors.lastname: Halldórsson
authors.forename: M
authors.initials: M
authors.lastname: Kjeld
authors.forename: G
authors.initials: G
authors.lastname: Thorgeirsson
mesh_terms: D019797:3-Iodobenzylguanidine / Q000494:pharmacology*; D001667:Binding, Competitive; D002478:Cells, Cultured; D002794:Choline / Q000493:pharmacokinetics; D006152:Cyclic GMP / Q000378:metabolism; D003562:Cytidine / Q000378:metabolism; D004730:Endothelium, Vascular / Q000187:drug effects*; D006632:Histamine / Q000494:pharmacology; D006634:Histamine H1 Antagonists / Q000494:pharmacology; D006801:Humans; D007294:Inositol / Q000378:metabolism / Q000493:pharmacokinetics; D007462:Iodobenzenes / Q000494:pharmacology; D009569:Nitric Oxide / Q000378:metabolism; D010743:Phospholipids / Q000032:analysis / Q000378:metabolism; D011433:Propranolol / Q000494:pharmacology; D011738:Pyrilamine / Q000378:metabolism; D011969:Receptors, Histamine H1 / Q000378:metabolism*; D012694:Serine / Q000493:pharmacokinetics; D014471:Umbilical Veins
chemical_list: D006634:Histamine H1 Antagonists; D007462:Iodobenzenes; D010743:Phospholipids; D011969:Receptors, Histamine H1; D009569:Nitric Oxide; D019797:3-Iodobenzylguanidine; D012694:Serine; D007294:Inositol; D003562:Cytidine; C008138:3-iodobenzylamine; D006632:Histamine; D011433:Propranolol; D006152:Cyclic GMP; D011738:Pyrilamine; D002794:Choline